the REALLY REALLY good news and the bad news (her2 stats outside clinical trials)

Lani · 08-10-2012, 03:50 PM

Good news: her2+ Stage I II III respond so well to herceptin their stats are
incredibly good

Bad news: % of Stage IVs whose first met is to the CNS is astonishingly high and even higher in those who had herceptin

SINCE SO FEW PROGRESSED TO STAGE IV THIS IS STILL GREAT NEWS AND SINCE HER2+ BRAIN METS RESPOND SO WELL TO SRS IT IS STILL RELATIVELY GOOD NEWS. NOW THEY NEED TO FIGURE OUT HOW TO PROTECT THE CNS (IE, WHETHER GIVING LAPATINIB OR OTHER DRUGS WHICH CROSS THE BBB PROPHYLACTICALLY) AND/ OR ON WHAT SCHEDULE /WHO SHOULD BE MRI'D PERIODICALLY TO CATCH THOSE CNS METS BEFORE THEY BECOME LARGE OR MULTIPLE

Curr Oncol. 2012 Aug;19(4):197-201.
Outcomes of women with early-stage breast cancer receiving adjuvant trastuzumab.
Seal MD, Speers CH, O'Reilly S, Gelmon KA, Ellard SL, Chia SK.
Source
BC Cancer Agency-Vancouver, Vancouver, BC.
Abstract
INTRODUCTION:
Large randomized trials assessing the benefit of adjuvant trastuzumab in early-stage breast cancer positive for the human epidermal growth factor receptor 2 (her2) have demonstrated a significant improvement in survival. The objective of the present study was to describe the outcomes of women who received adjuvant trastuzumab for her2-positive breast cancer in British Columbia since publicly funded population-based use was initiated in July 2005.
METHODS:
Women from British Columbia, newly diagnosed with stage i-iii breast cancer between July 2004 and December 2006, who were positive for her2 overexpression by immunohistochemistry (3+) or amplification by fluorescence in situ hybridization (ratio ≥ 2.0) were included in the study. Data were collected from the prospectively assembled BC Cancer Agency Outcomes Unit, with cases linked to the provincial pharmacy data repository to determine the proportion of women who received adjuvant trastuzumab.
RESULTS:
Our retrospective study identified 703 her2-positive patients, of whom 480 (68%) received trastuzumab. In patients receiving trastuzumab, the 2-year relapse-free survival was 96.1% [95% confidence interval (CI): 93.6% to 97.7%] and the overall survival was 99.3% (95% CI: 97.9% to 99.8%). Among node-negative and -positive patients, the 2-year relapse-free survival was 97.8% and 94.8% respectively (p = 0.09) for the trastuzumab-treated group and 90.9% and 77.3% (p = 0.01) for the group not receiving trastuzumab (n = 223). Site of first distant metastasis was the central nervous system in 19.5% of the entire cohort and in 37.5% of patients treated with trastuzumab.
DISCUSSION:
This population-based analysis of adjuvant trastuzumab use among Canadian women demonstrates highly favorable outcomes at the 2-year follow-up.
PMID: 22876145

Laurel · 08-10-2012, 05:30 PM

Lani,

Are there longer term stats yet? It seems we should have data for 6-8 years rather than just a 2 year follow up.

Lani · 08-11-2012, 01:29 PM

from the paper:
"The limitations of our study include a short follow-up (median of 2 years), but the 2-year point was when most of the adjuvant trastuzumab trials were first reported"
Median length of follow-up was 2.1 years and graphs in the article go out to 3 years.

Since historically according to Dr. Slamon her2+ breast cancers recurred prior to the time that the average of all types of bc recurred, good results @ 3 years would imply continued good results.

So far the No. American and HERA trials have not shown reversal of improved outlook of patients treated with herceptin ie, it is not just that they take longer to recur, so far they just do not recur) so it looks like the graphs which look great @ 3 years should continue to do so

THis study was somewhat confounded by adressing those who were offered herceptin late (WHENEVER after ASCO 2005 BRITISH COLUMBIA BEGAN TO OFFER THOSE WHO DID NOT GET IT A CHANCE TO GET IT) AND ONLY 28% OF THOSE WHO DID NOT GET HERCEPTIN EVEN GOT CHEMOTHERAPY!!!????

JUST SHOWS YOU HAVE TO READ THE SMALL PRINT AND NOT JUST THE ABSTRACT BEFORE CITING STUDIES AND ACCEPTING THEIR STATS AS THOSE THAT SHOULD BE DISSSEMINATED.

BUT I THINK THE TWO TAKE-HOME MESSAGES I IMPLIED PREVAIL"

1)THOSE WHO GET HERCEPTIN ADJUVANTLY STAGE 1-3 DO EXCEPTIONALLY WELL
CONSIDERING WHO THEY USED TO DO AND CONSIDERING THAT THEY NOW DO BETTER RATHER THAN WORSE THAN SOME OTHER SUBTYPES
2) THERE IS A CONCERN ABOUT HER2+ BREAST CANCER'S PREDELICTION FOR THE CNS AS A FIRST SITE OF METASTASIS, LACK OF GOOD SCREENING (PERHAPS FOLLOWING SERUM HER2 ECD IF IT WOULD BE FOUND TO BE SENSITIVE AND SPECIFIC ENOUGH TO HELP IN THIS REGARD OR SOME OTHER TEST AND GETTING BRAIN IMAGING IF IT INCREASES--SEEMS LIKE THE ACTUAL NUMBER OF THOSE GETTING HER2+ BRAIN METS AS FIRST SITE OF METASTASIS ALTHOUGH LARGER THAN PREVIOUSLY THOUGHT IS STILL SMALL WHEN YOU CONSIDER THE RESOURCES NECESSARY TO FOLLOW THEM WITH BRAIN IMAGING (AND WE DON'T EVEN REALLY KNOW HOW OFTEN).
THE PERCENT OF THOSE WITH BRAIN METS AS FIRST SITE OF METASTASIS IS CONSIDERABLE IN THOSE TREATED WITH HERCEPTIN SO LOOKING FOR WAYS TO DETECT THEM EARLY WHILE THEY ARE TREATABLE BY CYBER OR GAMMA KNIFE IS IMPERATIVE IT WOULD SEEM.

tricia keegan · 08-11-2012, 03:45 PM

Thanks Lani and this looks like good news but for those of us 6-8 years out who had Herceptin for early stage I feel maybe a standard brain scan at intervals would be the way to go?? I do intend asking my Onc for one when I next see her and thank you for the info!

Laurel · 08-11-2012, 06:19 PM

Thanks, Lani, that is encouraging news. I feel better now!

Rolepaul · 08-12-2012, 08:05 AM

This study and Lani's follow up says a lot. If you are node positive, and even more so at 3 or more nodes, the use of Herceptin has been very effective in the treatment of HER+ disease. Prior to the introduction of Herceptin, chances of being progression free two years after diagnosis was on the order of 77%. Those are still considered pretty good odds. The problem was that at five years it was on the order of 30% and at ten years the chances of being alive were minimal. I went through this with my mother between 1990 and 2000. Some of the first patients treated with Herceptin were the women treated at Balboa Naval Hospital in San Diego. There are a lot of untold stories out there. They knew about the risk of attacking the heart, and it did for my mother, which resulted in the pre-Herceptin treatment regimens that were not successful.

So the CNS band wagon that I am trying to get going for diagnosis and treatment might get another pony or two from this study. Diagnosis early means that the SRS treatment can get the ones that are observed. MRI scans or the brain and spine are very expensive, and may not be warranted for all that many cases.The goal should be to get an understanding of why it will sometimes go to the brain/spine, and why it will not in others. The second goal is to determine the effectiveness of Gamma/Cyber Knife followed by Tykerb/Xeloda in keeping them under check. The third goal is to use an effective treatment if the oral dose medications and Gamma/Cyber knife treatments are ineffective. As Nina and I walk down the path to the third goal, we understand the situation better than most. Each time we get bad news, we seem to have to chop another path through to a clear road. It would be nice for the information to have been there previously. Nina being an RN and with clinical trial certifiction, and my background in the Pharmaceutical business has been a blessing and a curse. We are able to know what has opportunities and the odds of existing treatments being effective. We have been lucky to convince our medical team to accept us in the decision making process, and willing to accept treatment regimens that others felt uncomfortable with. At the same time it is difficult to hear that doctors are not willing to listen to some patients that bring sound logic to bear for treatment. It is our hope that in the near future these three goals have defined paths. I will tell you that I do not think the state of knowledge right now is where it needs to be.

Nina's care is expensive. Since the initial Brain MRI scan showed a large lesion on 11/2/09 to today, the medical costs paid by insurance are probably close to $800K, with our own costs for deductibles, copays, parking, med copays, and travel representing about $50,000. We have spent the last eight months separated by 1200 (actually 1235) miles. I have flown there every two weeks since the middle of December 2011 and burned up all my vacation. It has stressed family relationships due to living at her brother's house. At the same time, Nina's life has been one that Nina looks and acts without disease, even going bak to her previous profession of therapeutic massage a few times per week. Would I do it again? There is no doubt I would. Can everyone do this? No way. I would like to not have individuals and families have to make these financial and emotional decisions, and for healthcare to treat HER+ before and after CNS involvement to be straight forward, affordable, and easy to have occur. This disease has none of that right now. I understand it will in the future. Nina and I made our future by taking the lead. I hope if you have disease and read it, you can get the better medical results that keep you from having to go down this path, but if that is not the case, it is our greatest belief that you do have hope; a true hope in getting better. Medical care for HER+ has advanced beyond anybody's expectations, but it still has a ways to go. It is our belief that we will get there in the next 5-10 years, but it will be at the cost of too many women and their families. This forum is a way to get things out in the open. Even the NEDs out there stay around and help those struggling. That is why this forum is important and I thank it for being there.

Too many words and thoughts for the forum. I hope that Nina continues to talk to NED. I wish all of the women on this forum could.

NEDenise · 08-12-2012, 09:03 AM

Paul,
Spoken from the heart...and heard the same way. Thanks for all your hard work to get the word out about these hope-filled treatment options.
All the best to you, and your precious wife, Nina!
Denise

tricia keegan · 08-12-2012, 01:10 PM

Sending my thanks and good wishes to you and Nina too Paul!

Lani · 08-12-2012, 02:02 PM

Rolepaul

DOn't know where you got your stats, but the stats I consider most important (although from a tiny series) are those for her2+ breast cancer that is DTC positive with her2+ dtc (tumor cells in bone marrow)

50& of those without herceptin treatment died within 5 years
90% of those without herceptin treatment died within 10 years

The vast majority of her2+ breast cancer patients DO NOT HAVE her2+ dtc,, but discovering those that do to be certain the treatment they receive clears their bone marrow (early studies showed chemo alone usually did not, though those studies did not look for her2 on the dtcs just dtcs in those whose primary were her2+) would seem to be the way to "cure" this disease.

Lymph node status may not turn out to be the be all and end all Just like histologic appearance it may turn out to be of historical interest only. It was all they used to have to go by. Now we know the biochemical pathways activated/deactivated are what make the tumor act the way it does and determines its prognosis, not what it looks like under the microscope. Similarly, all they used to have to guess at what made some tumors spread distantly was whether it had spread locally to the lymph nodes. We found out the characteristics which made it tend to go there(the lymph nodes via the lymph channelsO were different than those which encouraged hematogenous spread (via the blood) and similarly those attributes which make them settle successfully there vs the bone marrow, lung, liver, bone etc are seeming to turn out to be different. Yes, those tumors which were lymph node positive tended to have worse prognosis, but as systemic therapy seems to becoming better, the difference between prognosis in N0s and Nxs has diminished.

Now that we know more about the natural history of the disease, bc stem cells and all, it may be that her2+ cells in the bone marrow are much better predictors

CTCs so far have not been as accurate regarding prognosis. They may someday get to be, but THEY MAY NOT. What is floating around in the blood may turn out not to be as important as what has set up housekeeping in the bone marrow. Just because it can float around doesn't mean it can "nest and thrive"

I remain unable to understand why bone marrow testing is not being done, even in clinical trials, even in I-Spy.

RolePaul--how about a letter-writing campaign to Joel Gray/Laura Esserman (I-Spy) and Susan Love to see if we can include bone marrow testing in more clinical trials/biomarker discovery trials.

An ex neighbor of mine, in her 80s had a bone marrow aspirate done (was paid $100 and knew the result might help someone someday) and had truly minimal complaints thereafter--and it was done by a nurse practitioner in a clinic minor procedure room.

This should not break the bank or cause undue suffering and may give us invaluable information.

Off the soapbox again. I need to stay off it for at least a month now!

Rolepaul · 08-12-2012, 02:27 PM

Lani,
I think this whole site needs to write to I-spy for the Bone marrow analysis. I know that Nina is sampled every way you can think of but not for bone marrow aspiration.
The percents I quote are from researchers that are getting their stats together. The stats from twenty years ago for non-herceptin treatment were done from work that pushed Herceptin to market. I know they are out there but would have to use my resources that are in short supply right now. I am not one to back away a situation, but might have to put this one on hold for a few weeks due to too many irons in the fire.
I know that there are a lot of people to fight this disease, and there is money, and there are tools. We just do not seem to understand how to define the direction and what we want to have for progress. At this point, I want to have people treated, not without investigating, but also not letting people die by indecision and not trying. The lifeboat we put in the water is for the people on this boat trip, not on other boats. Research helps to get direction, but it does not help you to paddle. Right now, we might not see the island, but we can see the shorebirds. I want to paddle towards the shorebirds.

europa · 08-12-2012, 06:01 PM

Lani, if I ever get the opportunity to meet you, I owe you a fabulous bottle of champagne. You made my week with your post. The sats are just incredible. I have never felt so lucky to have Her2+ as I do today.

Ellie F · 08-13-2012, 03:33 AM

Lani
Don't get off the soapbox ever. It's because people like you and others arn't complacent that treatment and research moves ahead!

Ellie

Adriana Mangus · 08-15-2012, 12:00 AM

Dear Lani,

Thank you for the post. I always look forward to your postings, it's really interesting and so helpful to us Her2+ survivors. Its incredible the percentage of women who are alive thanks to Dr. Slamon.

I hope to meet him one day and personally thank him for the development of this wonderful drug.

In the meantime, I thank you for your devotion to our site.

Sincerely,

Adriana

Cure4Cat · 08-15-2012, 09:07 PM

Lani,

This is wonderful news. I can't thank you enough for all that you do. I saw my oncologist today and I am about to have my 2 year follow up scans in September. My doctor did not want to order a CT of the brain as I had one with my one year scans and another CT would expose me to more radiation. I am nervous as I know Herceptin does not cross the blood/brain barrier. Although I had a great response to chemo, I did not have a PCR and this has always made me nervous! Does anyone know how often we should be trying to get brain scans done? Sorry if I am going a bit off topic. I am not sure how to start my own thread.

Thanks,
Cat

Adriana Mangus · 08-15-2012, 11:49 PM

Hi Cat,

You need to speak with your doctor about getting a brain MRI at least once a year- I understand high risk patients, get it more often--, he should know the importance of it. I get mine once a year, right after January, it's easy to remember--a new year for me, stage IV cancer survivor.

Insist on it. Even if you have to change doctors, don't hesitate to speak with your doctor, if he's not listening to your needs, concerns and worries, you will be better off with someone new. Put your foot down, it's your life, if needed bring a friend with you.

Please keep us informed, we love you and care about your well being.

Love,

Adriana

bejuce · 08-16-2012, 10:19 AM

I'm going to start believing more that I'll be here for the long haul. I just passed my 3 year mark post surgery and so far so good. I may have some scans done next month to be sure. Should I push for a brain MRI as well? I'm ER+/PR-.

Thanks!!!

Laurel · 08-16-2012, 07:20 PM

Marsha,

Why not? If it provides peace of mind an MRI every few years or so, provided your Onc. authorizes it, may quiet those "nagging voices" in your head. If your insurance bulks just start complaining of a headache or migraine. They'll bounce a few sound waves off your noodle in a hurry, believe me. I had a migraine that lasted for nearly a year. They bounced my head found it to be a migraine and tried to get me to take anti-depressives. I opted for coconut oil instead which worked! Ha! Good luck with the anniversary scans next month!